Abstract
Synapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury. Although fundamental pathways that mediate intrinsic responses to neuronal injury have been defined, less is known about how synaptic partners adapt. We have investigated responses in the postsynaptic cell to presynaptic activation of the injury-related Dual Leucine Zipper Kinase pathway at the Drosophila neuromuscular junction. We find that the postsynaptic compartment reduces neurotransmitter receptor levels, thus depressing synaptic strength. Interestingly, this diminished state is stabilized through distinct modulations to two postsynaptic homeostatic signaling systems. First, a retrograde response normally triggered by reduced receptor levels is silenced, preventing a compensatory enhancement in presynaptic neurotransmitter release. However, when global presynaptic release is attenuated, a postsynaptic receptor scaling mechanism persists to adaptively stabilize this diminished neurotransmission state. Thus, the homeostatic set point of synaptic strength is recalibrated to a reduced state as synapses acclimate to injury.
Highlights
Synapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury
This process is conserved in rodents and humans[28,29], and is termed presynaptic homeostatic potentiation (PHP) because the expression mechanism of this form of plasticity is a presynaptic increase in neurotransmitter release
We considered the possibility that perhaps restoration of glutamate receptor (GluR) levels alone is sufficient to confer competence to transduce postsynaptic PHP signaling in hiw mutants
Summary
Synapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury. Neuronal expression of hiw restores normal synaptic strength and quantal size in hiw mutants[25], indicating that while the postsynaptic muscle does not itself experience hiwrelated signaling, a reduction in either the amount of glutamate released and/or the postsynaptic sensitivity to neurotransmitter occurs in response It remains unclear how synaptic function and plasticity change in response to presynaptic Wnd/ DLK signaling, a state in which injury-related signaling is active but before complete degeneration or loss of the presynaptic terminal has occurred. We have characterized synaptic structure, function, and plasticity at NMJs with active Wnd signaling in presynaptic neurons, with a particular focus on how the postsynaptic muscle responds This analysis has revealed that the postsynaptic muscle responds by diminishing GluR abundance and by silencing the retrograde homeostatic signaling system that would normally enhance presynaptic release following reduced GluR levels. This illuminates the distinct signaling systems targeted for modulation in the postsynaptic cell that stabilize a muted synaptic state in response to presynaptic Wnd signaling
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